Biology subjects

McAllister, S.

Publications and source records attributed to McAllister, S..

4 recordsLinked to original sources

bioRxiv2026

A Single-Cell Peripheral Immune Atlas Spanning High-Risk Lesions to Invasive Breast Cancer in Black and White Women

Black women are at risk for breast cancer nearly a decade before women of other racial groups for unclear reasons. Because immune responses influence cancer initiation and progression, we performed single-cell RNA sequencing of peripheral blood mononuclear cells from non-Hispanic Black (NHB) and non-Hispanic White (NHW) women with high-risk breast lesions, ductal carcinoma in-situ, and invasive breast cancer. Race-associated transcriptional differences were observed across all disease states and were most pronounced in invasive disease. Computational analyses, supported by flow cytometric protein analysis, revealed enrichment of chronic inflammation, immune regulatory programs, and immune aging pathways in NHB cancer patients, particularly in monocytes, dendritic cells, CD4+ T cells, and B cells. From these data, we derived a population-level immune signature (IMM-POP) comprising genes differentially enriched in this subset of immune cells from NHB breast cancer patients. IMM-POP correlates with an immunosuppressive signature in external breast cancer datasets. We thus provide a single-cell peripheral immune atlas integrating race and breast disease state. SignificanceThis study revealed race-specific peripheral immunity features in precancerous and invasive breast cancers: Black patients exhibited features of chronic inflammation and immune aging compared with White patients, suggesting immune weathering and providing insights for studying early onset of breast cancer in Black patients.

cancer biology↗

bioRxiv2022

Effect of acute ultraviolet radiation on Galleria mellonella health and immunity

For humans, acute and chronic overexposure to ultraviolet (UV) radiation can cause tissue damage in the form of sunburn and promote cancer(s). The immune-modulating properties of UV radiation and health-related consequences are not well known. Herein, we used the larvae of the wax moth (Galleria mellonella) to determine UV-driven changes in cellular components of innate immunity. From immune cell (haemocyte) reactivity and the production of antimicrobial factors, these insects share many functional similarities with mammalian innate immunity. After exposing insects to UVA or UVB, we monitored larval viability, susceptibility to infection, haemolymph (blood) physiology and faecal discharge. Prolonged exposure of larvae to UVB coincided with decreased survival, enhanced susceptibility to bacterial challenge, melanin synthesis in the haemolymph, compromised haemocyte functionality and changes in faecal (bacterial) content. We contend G. mellonella is a reliable in vivo model for assessing the impact of UV exposure at the whole organism and cellular levels.

cell biology↗

bioRxiv2021

Therapeutic reversal of prenatal pontine ID1 signaling in DIPG

Diffuse intrinsic pontine glioma (DIPG) is a highly aggressive brain tumor with rare survival beyond two years. This poor prognosis is largely due to the tumors highly infiltrative and invasive nature. Previous reports demonstrate upregulation of the transcription factor ID1 with H3K27M and ACVR1 mutations, but this has not been confirmed in human tumors or therapeutically targeted. We developed an in utero electroporation (IUE) murine H3K27M-driven tumor model, which demonstrates increased ID1 expression in H3K27M- and ACVR1-mutated tumor cells. In human tumors, elevated ID1 expression is associated with H3K27M/ACVR1-mutation, brainstem location, and reduced survival. The ID1 promoter demonstrates a similar active epigenetic state in H3K27M tumor cells and murine prenatal hindbrain cells. In the developing human brain, ID1 is expressed highest in oligo/astrocyte-precursor cells (OAPCs). These ID1+/SPARCL1+ cells share a transcriptional program with astrocyte-like (AC-like) DIPG cells, and demonstrate upregulation of gene sets involved with regulation of cell migration. Both genetic and pharmacologic [cannabidiol (CBD)] suppression of ID1 results in decreased DIPG cell invasion/migration in vitro and invasion/tumor growth in multiple in vivo models. CBD reduces proliferation through reactive oxygen species (ROS) production at low micromolar concentrations, which we found to be achievable in the murine brainstem. Further, pediatric high-grade glioma patients treated off-trial with CBD (n=15) demonstrate tumor ID1 reduction and improved overall survival compared to historical controls. Our study identifies that ID1 is upregulated in DIPG through reactivation of a developmental OAPC transcriptional state, and ID1-driven invasiveness of DIPG is therapeutically targetable with CBD. One Sentence SummaryThe transcription factor ID1 is upregulated in a subset of DIPG tumor cells, and ID1-driven invasiveness is therapeutically targetable with CBD.

cancer biology↗

bioRxiv2020

Targeting Reactive Aldehyde Detoxification by Aldehyde Dehydrogenase 2 (ALDH2) as a Treatment Strategy for Endometriosis

Endometriosis affects [~]176 million women worldwide, yet on average, women experience pain [~]10 years from symptom onset before being properly diagnosed. Standard treatments (drugs or surgery) often fail to provide long-term pain relief. Elevated levels of reactive aldehydes such as 4-hydroxynonenal (4-HNE) have been implicated in the peritoneal fluid of women with endometriosis and upon accumulation, reactive aldehydes can form protein-adducts and/or generate pain. A key enzyme in detoxifying reactive aldehydes to less reactive forms, is the mitochondrial enzyme aldehyde dehydrogenase-2 (ALDH2). Here, we tested the hypothesis that aberrant reactive aldehyde detoxification by ALDH2, underlies endometriosis and its associated pain. We determined, in the eutopic and ectopic endometrium of women with severe (stage IV) peritoneal endometriosis, that ALDH2 enzyme activity was decreased, which was associated with decreased ALDH2 expression and increased 4-HNE adduct formation compared to the eutopic endometrium of controls in the proliferative phase. Using a rodent model of endometriosis and an ALDH2*2 knock-in mouse with decreased ALDH2 activity, we determined that increasing ALDH2 activity with the enzyme activator Alda-1 could prevent endometriosis lesion development as well as alleviate pain-associated behaviors in proestrus. Overall, our findings suggest that targeting the ALDH2 enzyme in endometriosis may lead to better treatment strategies and in the proliferative phase, that increased 4-HNE adduct formation within the endometrium may serve as a less invasive diagnostic biomarker to reduce years of suffering in women. One Sentence SummaryALDH2 activity influences endometriosis and its associated pain.

physiology↗